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Genotyping for src-1 predicts for bone loss

a gene and bone loss technology, applied in the field of gene expression for src1, can solve the problems of increasing bone resorption and osteoclast numbers, and achieve the effect of increasing er activity and reducing er activity

Inactive Publication Date: 2009-10-29
BAYLOR COLLEGE OF MEDICINE
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Benefits of technology

The present patent provides a method for detecting a nucleic acid polymorphism in SRC-1, which is associated with an increased risk of osteopenia or osteoporosis. This method involves analyzing the nucleic acid polymorphism in SRC-1 in relation to a haplotype that is in linkage disequilibrium with the polymorphic site. The method can be used to detect the polymorphic site in a sample of bodily tissue or blood. The nucleic acid polymorphic site can be a single nucleotide polymorphism (SNP) or a combination of multiple SNPs. The method can also involve amplifying the genomic DNA and measuring the transcription or expression of the nucleic acid polymorphic site. The patent also provides a method for screening a SRC-1 protein variant for its coactivation potential. Overall, the method can help to identify individuals at risk for osteopenia or osteoporosis and provide a tool for personalized medicine.

Problems solved by technology

Decreased estrogen levels after menopause lead to an increase in osteoclast numbers and increased bone resorption.

Method used

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  • Genotyping for src-1 predicts for bone loss
  • Genotyping for src-1 predicts for bone loss
  • Genotyping for src-1 predicts for bone loss

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Embodiment Construction

[0041]To investigate the role of variations at the human SRC-1 locus in maintenance of BMD, we initially sought to identify SNPs in the coding regions of SRC-1. First, we carried out direct sequencing of all SRC-1 coding exons in 48 Caucasian and 48 African-American apparently normal individuals to identify novel SNPs, and to gain population-specific SNP information (Coriell Institute, NJ). From this effort we identified a total of six variants (Table 1). SNPs were identified through dbSNP (http: / / www.ncbi.nlm.nih.gov / projects / SNP / ) and by full exon sequencing of (Coriell samples. Our re-sequencing is listed as “Coriell re-sequencing” with AA representing African Americans and CA representing Caucasian Americans. (AGI ASP population is a mixture of African American and Caucasian samples. CEPH, HapMap-CEU, and AFD_EUR_PANEL represent populations of European descent. HapMap-HCB and AFD_CHN_PANEL populations are of Chinese descent. HapMap-YRI and AFD_AFR_PANEL are populations of Africa...

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Abstract

Osteoporosis is a common skeletal disease characterized by loss of bone mineral density (BMD) and increased risk of fracture. Osteoporosis most commonly occurs in postmenopausal women due to estrogen deficiency. We identified 3 genetic variants in steroid receptor coactivator 1 (SRC-1) that are significantly associated with a decrease in BMD in women. We characterized a functional variant in exon 18 of SRC-1 that is associated with increased loss of bone mineral density in women who received tamoxifen for treatment or prevention of breast cancer. In vitro experiments show that this variant decreases estrogen receptor alpha response (ER-alpha) to hormone, suggesting an attenuated response to endogenous and exogenous hormones in the bone of these women, and therefore a need for additional bone protective measures.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims under 35 U.S.C. § 119(e) the benefit of U.S. provisional patent application 61 / 073,421, filed 18 Jun. 2008. This application also claims under 35 U.S.C. § 119 (e) the benefit of U.S. provisional patent application 60 / 991,138, filed 29 Nov. 2007. The contents of the foregoing two provisional patent applications are hereby incorporated by reference in their entireties.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]This work was supported in part by a Pharmacogenetics Research Network Grant # U-01 GM61373 (DAF) which supports the Consortium on Breast Cancer Pharmacogenomics (COBRA). Other support came from Pilot Project (SO) from SPORE (CA58183) (CKO), Clinical Pharmacology training Grant 5T32-GM08425 from the National Institute of General Medical Sciences, National Institutes of Health (Bethesda, Md.), CA112403 (JX), GCRC # M01-RR000042 (University of Michigan), M01-RR13297, M01-RR020359 (George...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/68C12Q1/48
CPCC12Q1/6883C12Q2600/156C12Q2600/172C12Q2600/158C12Q2600/106
Inventor OESTERREICH, STEFFIRICHTER, ALEXANDRALEE, ADRIANOSBORNE, C. KENTMCGUIRE, SEAN E.HARTMAIER, RYAN
Owner BAYLOR COLLEGE OF MEDICINE
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